Population based standards for pulmonary function in non-smoking adults in Singapore

Abstract Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data ( n =406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20–79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), FEV₁/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore     

Detection of yellow fever virus in serum by enzyme immunoassay

Yellow fever (YF) virus is present in patient's blood during the acute phase of illness. Virus isolation and identification provide a potential method of early diagnosis, but available techniques are slow and require specialized materials and equipment. An alternative approach is direct detection of YF antigen in serum by means of an enzyme-linked immunosorbent assay (ELISA). An antigen-capture ELISA was developed, which used anti-YF antibodies, immobilized on a solid phase (polystyrene plates), to capture YF virus from serum samples. After addition of the virus-containing sample, anti-YF detecting antibody conjugated to alkaline phosphatase was added to detect viral antigen. Trials with various capture and detecting antibodies in systems employing purified YF 17D virus, led to the selection of: 1) two capture antibodies (pooled human serum containing high titer YF IgM antibodies and a type-specific YF monoclonal antibody), and 2) a detecting antibody conjugate consisting of monoclonal antibody broadly cross-reactive with all flaviviruses, purified by affinity chromatography, and conjugated to alkaline phosphatase. The limit of sensitivity in tests against purified YF 17D virus diluted in buffer or normal human serum was 10(3.0) - 10(3.6) PFU/0.05 ml or 0.007-0.029 microgram viral protein/0.05 ml. Sera obtained at intervals from rhesus and cynomolgus monkeys after infection with a wild YF virus strain were tested. The limit of sensitivity of the assay applied to viremic monkey serum was similar (approximately 3.5 log10PFU/0.05 ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

A further word of caution before using the internal mammary artery for coronary revascularization in patients with severe peripheral vascular disease!

Objectives: To characterize the clinical and angiographic characteristics of patients with collateralization from the internal mammary artery to the iliac artery. Background: The use of the internal mammary arteries for coronary revascularization has become the standard of care in coronary artery bypass grafting (CABG). However, in patients with aortoiliac disease, the internal mammary arteries may become a major collateral route to the lower extremities. Methods: A case series of 15 patients admitted for diagnostic coronary angiography were retrospectively identified, who were observed to have collateral flow from one or both internal mammary artery(ies) to an occluded or stenotic iliac artery. Results: The mean age was 63.2 ± 11.2 years; eight were men (53.3%). Coronary angiography was done as a perioperative evaluation for peripheral vascular surgery in three patients (20%) and was done because of cardiac symptoms or a positive thallium scan in 12 (80%). The finding that the mammary artery collateralized the iliac artery led to major treatment changes in all patients, seven (46.6%) who required CABG. In five patients (33%), use of one or both internal mammary artery(ies) for coronary grafts was avoided. CABG was deferred in one patient, whereas in another, percutaneous intervention in both iliac arteries preceded CABG using both mammary arteries. There was no incidence of postoperative acute lower extremity ischemia. Conclusions: Selective angiographic visualization of the internal mammary artery is an essential part of the preoperative evaluation in patients with severe peripheral vascular disease undergoing CABG. © 2009 Wiley‐Liss, Inc.     

Preclinical and Clinical Development of a YFV 17 D-Based Chimeric Vaccine against West Nile Virus

Substantial success has been achieved in the development and implementation of West Nile (WN) vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs) between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.     

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA⁺ type I, and CagA⁻ type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10⁷ CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10⁴–10⁵ CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a ≥100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2–3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.     

Safe splenoportography

The records of 37 patients who had undergone splenoportography, including one group of 12 who were studied before 1976 and a second group of 25 who were studied after 1977, were reviewed. The primary difference was that in the second group, the tract in the spleen was occluded with absorbable gelatin sponge (Gelfoam) plugs as the needle was withdrawn. In addition, there were minor changes in technique, such as changes in the needle puncture angle and entry site. When the new technique was used, there was a significant decrease in the complications traditionally associated with splenoportography. This procedure is safe and deserves to be considered the procedure of choice in patients in whom precise anatomic information is needed preoperatively that cannot be obtained with noninvasive procedures such as ultrasound or magnetic resonance imaging.     

Hippocampal formation and related structures of the limbic lobe: anatomic-MR correlation. Part II. Sagittal sections

Magnetic resonance (MR) images in the sagittal plane display the lengths of the parahippocampal gyrus, subiculum, dentate gyrus, hippocampus, fimbria, fornix, hippocampal fissure, choroidal fissure, and temporal horn, and the anatomic relationships of these structures to the surrounding brain. Correlation of these images with anatomic specimens provides criteria for identifying these structures confidently on routine clinical MR imaging.     

Serologic IgG response to urease in Helicobacter pylori-infected persons from Mexico.

Helicobacter pylori urease is required to counteract acidity during colonization of the stomach, and has been suggested as a major immunodominant antigen. The aim of this study was to determine the anti-urease response in a representative national serologic survey in Mexico. The population surveyed included persons 1-90 years of age from all socioeconomic levels and geographic zones of the country. Helicobacter pylori status was determined by ELISA serology. The IgG anti-urease was studied by ELISA using a recombinant apoenzyme. We found that 2,930 of the 7,720 infected patients (38%) were seropositive for IgG urease. The rate of IgG anti-urease positivity increased with age; in children < 10 years old it was < 20% and in persons > 40 years old it was > 50%. Age and a region with a high level of development were risk factors for seropositivity, whereas gender, educational level, crowding, and socioeconomic level were not associated with seropositivity. In conclusion, in natural infection with H. pylori, the response to urease is poor, mainly during the first years of infection. This inconsistent immune response to the enzyme may favor persistence of infection. A vaccine eliciting a consistent anti-urease response might overcome immune evasion and enhance clearance of bacteria after exposure.